Olezarsen in Patients with Hypertriglyceridemia at High Cardiovascular Risk: Rationale and Design of the Essence-TIMI 73b Trial.

Background: Elevated triglycerides are an important risk factor for atherosclerosis. However, the magnitude of triglyceride lowering with currently available therapies is modest and the impact of triglyceride-lowering on atherosclerosis remains undefined. Olezarsen is an antisense oligonucleotide (ASO) targeting mRNA for apolipoprotein C-III (apoC-III), an inhibitor of triglyceride clearance.

Design and Rationale of the CORE -TIMI 72a and CORE2 -TIMI 72b Trials of Olezarsen in Patients with Severe Hypertriglyceridemia.

Severe hypertriglyceridemia (HTG), defined as a serum triglyceride (TG) concentration ≥500 mg/dl, is present in approximately 1 in every 500 individuals and carries direct clinical consequences, including pancreatitis, which can be life-threatening. Olezarsen is an investigational antisense oligonucleotide targeted to the mRNA for apolipoprotein C-III (apoC-III), a protein known to impair TG clearance by inhibiting lipoprotein lipase and the hepatic uptake of triglycerides and triglyceride-rich remnants. Olezarsen has been evaluated in patients with predominantly moderate HTG (150-499 mg/dl) and a rare genetic condition known as Familial Chylomicronemia Syndrome (FCS), with TG lowering effects of 53% and 44%, respectively, and reductions in pancreatitis among the FCS population.

[Retracted] IQGAP1 plays an important role in the cell proliferation of multiple myeloma via the MAP kinase (ERK) pathway.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that certain discrete western blot data shown in the RT‑qPCR blots in Figs. 1A and 2A, and western blot data in Fig. 5 were strikingly similar to data that had already appeared in previously published papers in different journals written by different authors at different research institutes.

A Knowledge-Guided Graph Learning Approach Bridging Phenotype- and Target-Based Drug Discovery.

Discovering therapeutic molecules requires the integration of both phenotype-based drug discovery (PDD) and target-based drug discovery (TDD). However, this integration remains challenging due to the inherent heterogeneity, noise, and bias present in biomedical data. In this study, Knowledge-Guided Drug Relational Predictor (KGDRP), a graph representation learning approach is developed that effectively integrates multimodal biomedical data, including network data containing biological system information, gene expression data, and sequence data that incorporates chemical molecular structures, all within a heterogeneous graph (HG) structure.

Discovery of antimicrobial peptides with notable antibacterial potency by an LLM-based foundation model.

Large language models (LLMs) have shown remarkable advancements in chemistry and biomedical research, acting as versatile foundation models for various tasks. We introduce AMP-Designer, an LLM-based approach, for swiftly designing antimicrobial peptides (AMPs) with desired properties. Within 11 days, AMP-Designer achieved the de novo design of 18 AMPs with broad-spectrum activity against Gram-negative bacteria.

Dual Flexible Prescribed Performance Control of Input Saturated High-Order Nonlinear Systems.

This article first presents a dual flexible prescribed performance control (DFPPC) approach of input saturated high-order nonlinear systems (IS-HONSs). Compared to the existing PPC approaches of IS-HONSs, under which the performance constraint boundaries (PCBs) are usually fixed and bounded, resulting in a restriction of the initial error in the algorithm implementation; in addition, the coupling relationship between performance constraints and input saturation is usually ignored, resulting in the methods are very fragile when input saturation occurs. By designing the novel tensile model-based PCBs that depend on output and input constraints, the proposed DFPPC method provides sufficient resilience for both the initial conditions and the input saturation, so that the proposed DFPPC method can not only be suitable for multiple types of initial errors by adjusting the parameters, including , , and , where , and denote the initial PCBs; but also can achieve a good balance between input saturation and performance constraints, i.

Spatiotemporal Imputation of Traffic Emissions With Self-Supervised Diffusion Model.

The comprehensive regulatory oversight of traffic emissions frequently encounters the missing not-at-random (MNAR) pattern, characterized by the long-term block missing in adjacent road segments, arising from insufficient monitoring points and nonuniform spatiotemporal distribution. The spatiotemporal block missing simultaneously disrupts the spatiotemporal correlation, introducing significant biases in spatiotemporal modeling for incomplete data. The emerging diffusion model recovers the information of the missing regions in a self-supervised manner and focuses on the generation process of the missing regions to address biases.

Syn-MolOpt: a synthesis planning-driven molecular optimization method using data-derived functional reaction templates.

Molecular optimization is a crucial step in drug development, involving structural modifications to improve the desired properties of drug candidates. Although many deep-learning-based molecular optimization algorithms have been proposed and may perform well on benchmarks, they usually do not pay sufficient attention to the synthesizability of molecules, resulting in optimized compounds difficult to be synthesized. To address this issue, we first developed a general pipeline capable of constructing functional reaction template library specific to any property where a predictive model can be built.

Robust protein-ligand interaction modeling through integrating physical laws and geometric knowledge for absolute binding free energy calculation.

Accurate estimation of protein-ligand (PL) binding free energies is a crucial task in medicinal chemistry and a critical measure of PL interaction modeling effectiveness. However, traditional computational methods are often computationally expensive and prone to errors. Recently, deep learning (DL)-based approaches for predicting PL interactions have gained enormous attention, but their accuracy and generalizability are hindered by data scarcity.

Novel injectable self-healing bifunctionalized chitosan hydrogel with cell proliferation and antibacterial activity for promoting wound healing.

Wound healing is a complex and continuous process and there is an urgent need to develop effective, functional wound dressings to accelerate wound healing. In this study, we developed an injectable self-healing dual-modified chitosan composite hydrogel, referred to as CSTA@Gel. This hydrogel exhibits good properties, including effective tissue adhesion, rapid hemostatic ability, and good cytocompatibility and hemocompatibility.

Comparative Efficacy of Glucagon-Like Peptide 1 Receptor Agonists for Cardiovascular Outcomes in Asian Versus White Populations: Systematic Review and Meta-analysis of Randomized Trials of Populations With or Without Type 2 Diabetes and/or Overweight or Obesity.

Background: Cardiovascular outcome trials (CVOTs) suggest glucagon-like peptide 1 receptor agonists (GLP-1RAs) provide greater cardiovascular (CV) benefits in Asian compared with White individuals.

Purpose: Compare CV efficacy of GLP-1RAs between Asian and White individuals.

Data Sources: Systematic review of PubMed and ClinicalTrials.

SIRT6 Ameliorates Cancer Cachexia-Associated Adipose Wasting by Suppressing TNFR2 Signalling in Mice.

Background: Cachexia is a wasting syndrome associated with imbalanced energy metabolism and loss of adipose and muscle tissues and contributes to morbidity and mortality in ageing as well as in patients with severe chronic diseases, including cancer. At present, there are no treatments addressing cachexia that have reached validation to be used in the clinic. In this study, we investigate the protective role of SIRT6, an important regulator of energy homeostasis and health preservation, against Lewis lung carcinoma (LLC)-induced cachexia.

Electrical impedance tomography-guided positive end-expiratory pressure titration for perioperative oxygenation and postoperative pulmonary complications: A systematic review and meta-analysis.

Background: The electrical impedance tomography (EIT)-guided individual positive end-expiratory pressure (PEEP) approach is a noninvasive, radiation-free, and straightforward strategy. However, its validity to prevent postoperative complications remains unclear. To determine whether the EIT-guided PEEP titration in surgery has a higher oxygenation index and lower postoperative complications incidence in patients, we performed a meta-analysis to assess the efficacy.

[Effects of serum vitamin K levels in early pregnancy on pregnancy-related diseases and adverse pregnancy outcomes].

Objective: To explore the relationship between vitamin K levels and pregnancy-related diseases and adverse pregnancy outcomes in early pregnancy.

Methods: A convenience sampling method was used to select 367 women in early pregnancy who were enrolled in the Shunyi Women's and Children's Hospital of Beijing Children's Hospital from October 2018 to September 2019. Basic information such as age, height, and pre-pregnancy weight of the respondents was collected, blood samples were taken and the concentration of vitamin K(vitamin K1, MK-4 and MK-7) was measured by liquid chromatography tandem mass spectrometry(LC-MS/MS).

The role of Lactobacterium plantarum in solid-state fermentation of Astragalus membranaceus for broiler chicken feed.

The purpose of this study was to examine the fermentation of A. membranaceus by L. plantarum and its effects on broiler chickens.

Geometrical Features of Subbasal Corneal Whorl-like Nerve Patterns in Dry Eye Disease: An In Vivo Confocal Microscopy Study.

Purpose: To investigate the geometrical feature of the whorl-like corneal nerve in dry eye disease (DED) across different severity levels and subtypes and preliminarily explore its diagnostic ability.

Design: Cross-sectional study.

Participants: The study included 29 healthy subjects (51 eyes) and 62 DED patients (95 eyes).

Serum and urine eosinophil-derived neurotoxin (EDN) levels predict biologic response in severe asthma.

Background: Eosinophils are crucial in allergic inflammation, and their correlation with asthma severity has made them a focal point in predicting treatment outcomes. Blood eosinophil count is a commonly utilized marker. However, its limitations have prompted alternative biomarker exploration, such as eosinophil-derived neurotoxin (EDN).

Research on technological innovation decision-making considering government subsidies and corporate reputation.

Aiming at the information asymmetry between pharmaceutical enterprises' technological innovation decisions and government subsidy strategy, this paper establishes a differential game model consisting of the government and a single pharmaceutical company, proposes three different government subsidy strategies, and obtains an equilibrium solution with the help of the Hamilton-Jacobi-Bellman equation, taking into consideration of the transmission effect of the enterprise's reputation. First, the innovation decisions of pharmaceutical firms without government subsidies are analysed, and based on this, the optimal strategies with government subsidies for non-cooperative pacts and cooperation between the government and enterprises are analysed separately. In addition, the effects of different subsidy strategies on the government's investment efficiency, corporate reputation, and the choice of corporate innovation strategies are compared, and the results are verified by numerical analysis.

Predictive Value of Left Atrial Strain for Thrombotic Events in Hypertrophic Cardiomyopathy without Atrial Fibrillation.

Purpose To assess the predictive value of left atrial (LA) fast long-axis strain derived from cardiac MRI for thrombotic events (TEs) in individuals with hypertrophic cardiomyopathy (HCM). Materials and Methods This secondary analysis of an ongoing prospective trial (Chinese Clinical Trial Registry: ChiCTR1900024094) included consecutive participants with HCM without atrial fibrillation (AF) who underwent cardiac MRI from January 2012 to December 2020. The LA fast long-axis strain was obtained by semiautomatically tracking the distance between the atrioventricular junction and the midposterior LA wall.

Highly efficient construction of monkey blastoid capsules from aged somatic cells.

Blastoids-blastocyst-like structures created in vitro-emerge as a valuable model for early embryonic development research. Non-human primates stem cell-derived blastoids are an ethically viable alternative to human counterparts, yet the low formation efficiency of monkey blastoid cavities, typically below 30%, has limited their utility. Prior research has predominantly utilized embryonic stem cells.

The effect of registered nurse staffing and skill mix on length of stay and hospital costs.

Background: Sepsis is a common cause of hospitalization among Medicare beneficiaries, often leading to prolonged hospital stays and high costs.

Purpose: To estimate the impact of registered nurse (RN) staffing and skill mix on hospital lengths of stay and associated costs for Medicare beneficiaries with sepsis.

Methods: A retrospective, cross-sectional analysis was conducted using 2018 data from 2,107 acute care hospitals, including 653,496 patients with sepsis.

mTOR Inhibitor Everolimus Modulates Tumor Growth in Small-Cell Carcinoma of the Ovary, Hypercalcemic Type and Augments the Drug Sensitivity of Cancer Cells to Cisplatin.

: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and aggressive cancer with a poor prognosis and limited treatment options. Current chemotherapy regimens are predominantly platinum-based; however, the development of platinum resistance during treatment significantly worsens patient outcomes. Everolimus, an mTOR inhibitor, has been widely used in combination cancer therapies and has successfully enhanced the efficacy of platinum-based treatments.

First Molecular Identification of spp. in Sheep, Beef Cattle, and Dairy Cattle in Shanxi Province, North China.

spp. are common zoonotic intestinal protozoa, which can lead to serious intestinal diseases in both humans and animals through fecal-oral transmission, leading to significant economic losses and public health challenges. To reveal the prevalence of in sheep and cattle in Shanxi Province, North China, fecal samples were collected from 311 sheep, 392 dairy cattle, and 393 beef cattle from three representative counties in the northern, central, and southern regions of Shanxi Province.

Cognitive function differs across healthy lifestyle behavior profiles: a 10-year population-based prospective cohort study.

Background: Modifiable lifestyle behaviors significantly influence the risk of cognitive impairment. However, the cumulative effects of multidimensional lifestyle profiles on cognitive function remain poorly understood, as most studies examine individual lifestyle behaviors in isolation. This study aimed to identify distinct profiles of individuals based on healthy lifestyle behaviors and to examine associations between these profiles and cognitive function in older Chinese adults.